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转录因子Otx1在大脑皮质第5皮层锥体神经元中特异性表达。该研究利用全细胞膜片钳记录技术和神经元三维形态模拟重构及定量分析平台探讨Otx1在小鼠癫痫样行为中的潜在作用机制。结果表明,在大脑皮质运动区第5皮层锥体神经元中鉴定到四种不同放电类型的神经元,即固有爆发式、节律性振荡爆发式、适应性规律式及紧张性放电型。与对照相比,Otx1突变小鼠中规律式放电神经元的比例显著升高,而爆发式放电神经元的比例显著减少并表现出增强的兴奋性。此外,Otx1突变促使神经元动作电位(action potential,AP)阈值、输入阻抗及快速后超极化电位都显著降低,进而使其兴奋性增强。Otx1突变降低神经元基树突形态结构复杂性,主要表现为基树突表面积、体积、分节表面积及分节体积的显著降低。可见,Otx1突变导致大脑皮质运动区第5皮层锥体神经元生理功能的改变可能是小鼠癫痫样行为的潜在原因。
The transcription factor Otx1 is specifically expressed in the fifth cortical neurons of the cerebral cortex. This study investigated the potential mechanism of Otx1 in the epileptiform behavior of mice using whole-cell patch clamp recording technology and neuronal three-dimensional morphological reconstruction and quantitative analysis platform. The results showed that four types of neurons of different discharge types were identified in the pyramidal neurons of the 5th cortex in the motor cortex of the cerebral cortex, namely inherent burst, rhythmic oscillation burst, adaptive regularity and tension discharge. The proportion of regular discharge neurons in Otx1 mutant mice was significantly increased compared to the control, while the proportion of blast-discharge neurons was significantly reduced and showed enhanced excitability. In addition, Otx1 mutation significantly reduced the threshold of neuron’s action potential (AP), the input impedance and the hyperpolarization potential after fast, which further enhanced its excitability. The Otx1 mutation reduced the structural complexity of neuronal dendrites, which was mainly manifested by the marked reduction of basal dendrites’ surface area, volume, sectional area and sectional volume. It can be seen that the alteration of the physiological function of pyramidal neurons in the fifth cortex in the motor cortical area by Otx1 mutation may be the underlying cause of epileptiform behavior in mice.